Tumor angiogenesis has recently been shown to play essential role in tumor growth and metastases. Angiogenesis inhibitors are a promising new class of drugs with great potential for the treatment of human cancers, as well as other diseases. However, since these drugs may have minimal toxicities and may induce tumor dormancy or prolonged stable disease rather than tumor shrinkage, it is unclear how to determine whether these agents and the selected doses are in fact biologically active before committing to large phase III studies. The overall goal of this proposal is to evaluate in the clinical setting a novel and promising surrogate bio-marker of angiogenesis that is both technically straightforward and biologically relevant-- the skin wound angiogenesis assay. This assay utilizes a 4mm punch biopsy, which produces a potent angiogenic stimulus and also allows clear visualization of new vessels growing into the dermis. The proliferating neo- vasculature is followed non-invasively over a two week period by direct microscopy and by scanning laser Doppler, which measures micro-vessel blood in the newly developing vasculature. This assay has been evaluated in a study of healthy volunteers; it appears to be very well tolerated and is highly reproducible. This assay is based upon four principles. First, wound angiogenesis is regulated by fundamentally the same factors and pathways that regulate tumor angiogenesis. Second, this assay provides a global readout of a drug's anti-angiogenic effect rather than an analysis of only one specific pathway. This information may be particularly useful in helping to dissect and analyze multiple angiogenesis regulatory pathways that may be altered by a specific anti-angiogenic agent. Third, the most likely toxicity of anti-angiogenesis agents may be altered wound healing or a greater bleeding risk due to increased capillary fragility. These effects should also be detectable with this assay. Lastly, this assay is practical and convenient to use in the clinical setting, which is a critical requirement for any surrogate bio-marker assay. The specific goals of this study are: 1) To evaluate the feasibility and tolerability of this novel bio-marker assay in clinical phase I, II, and III trials of anti-angiogenesis agents. 2) To quantitate the anti-angiogenic effect of promising anti- angiogenesis agents using this novel biomarker assay. 3) To evaluate the relationship between drug dose and pharmacokinetic parameters and anti-angiogenic effect using this novel biomarker assay. 4) To evaluate several potential refinements of this normal wound angiogenesis assay in healthy volunteers, and incorporate these refinements in to patient studies involving novel anti-angiogenesis agents.